Thrombotic microangiopathic hemolytic anemia (TMHA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and kidney involvement. It presents as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TMHA has been considered to occur only rarely in systemic lupus erythematosus (SLE). However, there has been an increase in the reporting of this association in recent years, and autopsy studies have suggested that TMHA may be underdiagnosed in SLE because of the similarity in symptoms. We report four patients with SLE-related TMHA and describe 24 more patients from a literature review. All patients were women, 50% had active SLE, 89% presented as TTP, and 11% presented as HUS. Those patients with active SLE had low complement levels. Antiphospholipid antibodies or lupus anticoagulant were positive in 5 of 8 cases. Patients treated with plasma infusions or plasmapheresis had a lower mortality rate at 25% compared with 57% mortality in patients who were not treated with plasma infusions or plasmapheresis. It is suggested that TMHA should be considered in any SLE patient presenting with neurological symptoms or renal failure associated with fever, hemolytic anemia, and thrombocytopenia. Early recognition and appropriate therapy with plasmapheresis may improve prognosis.